Abstract

Ascorbate (AsA), or vitamin C, is a central redox metabolite that functions as an antioxidant, enzyme cofactor, and electron donor. Its cellular function depends not only on biosynthesis or dietary uptake, but also on rapid recycling from its oxidized forms, monodehydroascorbate (MDHA) and dehydroascorbate (DHA). This requirement is especially evident in high-demand systems such as plant chloroplasts, which face continuous photosynthetic reactive oxygen species (ROS) production under illumination, and human neutrophils, which accumulate millimolar ascorbate to withstand NADPH oxidase-driven oxidative bursts in pathogen defense. Here, we revisit ascorbate recycling from a sulfur-centered perspective. Historical studies of plant, animal, and solution-chemistry pathways show that many DHA-reducing systems converge on sulfur chemistry, including glutathione (GSH), cysteine-dependent enzymes, H2S, and modified thiols. We propose that ascorbate recycling is organized as a multilayered system in which nonenzymatic reactions are accelerated by enzymes, localized within cellular or extracellular compartments, and integrated with broader NAD(P)H-, glutathione-, sulfur-, and diet-dependent redox networks. Within this framework, the AsA/DHA couple can be viewed as a molecular redox capacitor that buffers transient oxidative pressure. Reactive sulfur species (RSS), including persulfides and polysulfides, represent chemically plausible but experimentally unresolved contributors to DHA reduction.

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